We have analyzed plasma samples from approximately 200 of the participants enrolled in IRB-approved protocol 2003-086 with diagnoses of Ehlers Danlos Syndrome, Fibromuscular Dysplasia and Marfan Syndrome. These diagnoses are associated with adverse cardiovascular events and early vascular aging causing premature death. The endocrine markers of interest include free and total testosterone, sex hormone binding globulin, estrone, estrodiol, IGF-1, LH and FSH. Approximately 30% of men with Ehlers Danlos syndrome and Marfan syndrome have abnormally low testosterone levels. Corresponding LH and FSH values are low, indicating abnormal pituitary function as opposed to gonadal dysfunction. Elevated Sex Hormone Binding Globulin is seen in women will all the above diagnoses. Children with connective tissue disorders have low circulating values of IGF-1. In addition, patients with the vascular form of Ehlers Danlos have elevated leptin levels as compared to age and sex matched controls. The endocrine abnormalities are correlated with low bone density and poor cardiovascular prognosis. We plan to investigate the pathological mechanisms of these findings. It is not yet clear that these abnormalities are protective responses to the underlying vascular pathology versus causally involved in the development of the adverse vascular events. The decision to correct the abnormalities is dependent on better understanding of the mechanisms of these findings.